The goal of this research project is to provide a better understanding of the control of eye movements by integrating the known physiology and anatomy of neurons in the goldfish with the developmental and molecular potential of the zebrafish model system. The structural blueprint responsible for all oculomotor behaviors appears to be the result of highly conserved genetic and anatomical profiles that create 8 embryonic hindbrain compartments. It is hypothesized that single genes essential for the development and function of specific eye movement-related neurons and circuits can be analyzed by measurement of oculomotor behavior in zebrafish larvae and mutants. The central processing of visual and vestibular sensory signals that produce horizontal eye movements depends on two brainstem nuclei referred to as neural integrators since they convert either head acceleration or velocity-related inputs to eye velocity and eye position-related signals. In conjunction with cerebellar processing, these signals are necessary for oculomotor performance and learning. Strikingly, there appear to be only two precerebellar pathways uniquely related to horizontal oculomotor behavior in the goldfish. These comprise the eye velocity nucleus that forms the mossy fiber pathway and the inferior olive that forms the climbing fiber pathway to Purkinje cells that directly control specific subgroups of vestibuloocular neurons. This project will utilize contemporary computational and electrophysiological approaches to parse out the contributions of intrinsic 'cellular' versus extrinsic 'network' signal processing capabilities of these two precerebellar pathways by employing multiple intra- and extracellular recording in goldfish and noninvasive confocal and two photon laser scanning microscopy in zebrafish. A second set of aims will focus on the morphology and genetic analysis of the above mentioned subgroups in embryonic zebrafish thereby allowing structural and behavioral analysis of relevant single gene mutations. The long term goal of the research project will be to characterize candidate genetic pathways that are essential for defining the operation of neurons and circuits responsible for horizontal oculomotor signal processing and motor learning.